Federal University of Santa Catarina.
J Pharm Pharm Sci. 2021;24:23-36. doi: 10.18433/jpps31349.
Current therapies for acute leukemias (ALs) are associated with severe adverse reactions and high relapse rates, which makes the search for new antileukemic agents a necessity. Therefore, the aim of this study was to evaluate the effects of a new sulfonamide, S1, in AL cells K562 and Jurkat.
The cytotoxic activity of S1 was assessed using MTT method. The involvement of apoptosis in the mechanism of cell death was assessed by flow cytometry and fluorescence microscopy.
Our results demonstrated that S1 induced morphological changes suggestive of apoptosis in both K562 and Jurkat cells. Additionally, S1 was not cytotoxic to normal erythrocytes and mononuclear cells and had a highly selective cytotoxicity for AL lineages. The mechanisms of cell death induced by S1 in K562 cells involves cell cycle arrest at G2/M phase and the activation of both extrinsic and intrinsic apoptosis, with an increased FasR and AIF expression and the loss of mitochondrial potential. As for Jurkat, we observed cell cycle blockade at G0/G1 phase, phosphatidylserine exposure and the involvement of intrinsic apoptosis only, with mitochondrial potential loss and a reduced expression of Survivin. Although sulfonamide S1 did not altered Bcl-2 and Bax expression in AL cell lines, it was able to activate caspase-3 in K562 cells.
Our results suggest that sulfonamide S1 may be a promising candidate for the development of new drugs for the treatment of ALs.
目前治疗急性白血病（ALs）的方法会引起严重的不良反应和高复发率，因此需要寻找新的抗白血病药物。本研究旨在评估新型磺胺 S1 在 AL 细胞系 K562 和 Jurkat 中的作用。
采用 MTT 法评估 S1 的细胞毒性。通过流式细胞术和荧光显微镜评估细胞凋亡在细胞死亡机制中的作用。
我们的结果表明，S1 诱导 K562 和 Jurkat 细胞发生凋亡样形态变化。此外，S1 对正常红细胞和单核细胞无细胞毒性，对 AL 细胞系具有高度选择性的细胞毒性。S1 在 K562 细胞中诱导的细胞死亡机制涉及 G2/M 期细胞周期阻滞和外源性和内源性凋亡的激活，FasR 和 AIF 表达增加，线粒体膜电位丧失。对于 Jurkat，我们观察到 G0/G1 期细胞周期阻滞、磷脂酰丝氨酸暴露和仅涉及内源性凋亡，线粒体膜电位丧失和 Survivin 表达降低。虽然磺胺 S1 没有改变 AL 细胞系中 Bcl-2 和 Bax 的表达，但它能够激活 K562 细胞中的 caspase-3。
我们的结果表明，磺胺 S1 可能是开发治疗 ALs 新药的有前途的候选药物。
